Project description
Myelin formation and regeneration for effective therapies
Myelination is vital for the vertebrate nervous system. In multiple sclerosis (MS), myelin damage disrupts nerve conduction and leads to neuronal loss. Understanding how myelin forms and is repaired is essential for effective therapies, especially regarding the role of paranodes, whose molecular organisation is still unclear. Supported by the Marie Skłodowska-Curie Actions programme, the MInDRe project will use zebrafish models and advanced in vivo proximity proteomics techniques to conduct the first proteomic screen of the paranodal proteome during myelin growth and repair. Candidate regulators will be validated using CRISPR-based gene targeting in zebrafish and tested for conservation in mammals. This approach will help identify key regulators of paranodal dynamics and explain myelin formation and regeneration.
Objective
Accurate myelination of neuronal circuits is essential for the efficient function of the vertebrate nervous system, as the exact amount of myelin ensheathing an axon influences the timing and energy efficiency of neurotransmission. Its importance becomes evident in multiple sclerosis (MS), when myelin damage disrupts conduction and ultimately causes long-term neuronal loss. Although remyelination occurs, regenerated sheaths remain abnormally thin and short, failing to fully restore function. Promoting efficient myelin formation and repair is therefore a critical therapeutic target - yet the molecular mechanisms regulating accurate sheath growth in development and regeneration remain poorly understood. I propose that dynamic regulation of proteins along the axon-myelin interface—the direct contact site between axons and myelin—is critical for accurate myelin formation and repair. In particular, paranodes, specialised adhesion domains at this interface, are among the first structures disrupted in MS; and mutations in paranodal proteins cause severe developmental myelin growth defects reminiscent of MS pathology. However, the molecular organisation and dynamic regulation of paranodes remain largely unknown, due to technical limitations in profiling this subdomain in vivo. To address this, I will combine zebrafish models with newly developed tools for in vivo proximity proteomics and endogenous protein reporters. This approach enables the first in vivo proteomic screen to specifically profile the paranodal proteome during myelin growth and repair. Candidate regulators will be validated using CRISPR-based gene targeting in zebrafish and tested for conservation in mammalian systems. By integrating sub-cellular proteomics with advanced live-imaging and careful cross-species validation, this project will identify key-regulators of paranodal dynamics; and provide valuable insights into the mechanism underlying efficient myelin formation and regeneration after damage.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- engineering and technology environmental engineering ecosystem-based management climatic change mitigation
- medical and health sciences basic medicine neurology multiple sclerosis
- medical and health sciences basic medicine pathology
You need to log in or register to use this function
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
-
HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
See all projects funded under this programme
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
See all projects funded under this funding scheme
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2025-PF
See all projects funded under this callCoordinator
Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
EH8 9YL Edinburgh
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.